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Blind predictions of octanol/water partition coefficients and pKa at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. Octanol/water partition coefficients were predicted from solvation free energies computed using electronic structure calculations with the SM12, SM8 and SMD solvation models. Within these calculations we compared the use of gas- and solution-phase optimized geometries of the solute. Based on these calculations we found that in general the use of solution phase-optimized geometries increases the affinity of the solutes for water as compared to octanol, with the use of gas-phase optimized geometries resulting in the better agreement with experiment. The pKa is computed using the direct approach, scaled solvent-accessible surface model, and the inclusion of an explicit water molecule, where the latter two methods have previously been shown to offer improved predictions as compared to the direct approach. We find that the use of an explicit water molecule provides superior predictions, and that the predicted macroscopic pKa is sensitive to the employed microstates., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Blind predictions of octanol/water partition coefficients at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. The octanol/water partition coefficients were predicted using solvation free energies computed using molecular dynamics simulations, wherein we considered the use of both pure and water-saturated 1-octanol to model the octanol-rich phase. Water and 1-octanol were modeled using TIP4P and TrAPPE-UA, respectively, which have been shown to well reproduce the experimental mutual solubility, and the solutes were modeled using GAFF. After the close of the SAMPL7 challenge, we additionally made predictions using TIP4P/2005 water. We found that the predictions were sensitive to the choice of water force field. However, the effect of water in the octanol-rich phase was found to be even more significant and non-negligible. The effect of inclusion of water was additionally sensitive to the chemical structure of the solute., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Disulfide bonds play a crucial role in folding and structural stabilization of monoclonal antibodies (mAbs). Disulfide bond reduction may happen during the mAb manufacturing process, resulting in low molecular weight species and possible failure to meet product specifications. Although many mitigation strategies have been developed to prevent disulfide reduction, to the best of our knowledge, reforming disulfide bonds from the reduced antibody in manufacturing has not previously been reported. Here, we explored a novel rescue strategy in the downstream process to repair the broken disulfide bonds via in-vitro redox reactions on Protein A resin. Redox conditions including redox pair (cysteine/cystine ratio), pH, temperature, and reaction time were examined to achieve high antibody purity and a high reaction rate. Under the optimal redox condition, >90% reduced antibody could be reoxidized to form an intact antibody on Protein A resin in an hour. In addition, this study showed high flexibility on the range of the intact mAb fraction in the initial reduced mAb sample (the lower limit of intact mAb faction could be 14% based on the data reported in this study). Furthermore, a kinetic model based on elementary oxidative reactions was constructed to help optimize the reoxidation conditions and to predict product purity. Together, the deep understanding of interchain disulfide bond reoxidation, combined with the predictive kinetic model, provided a good foundation to implement a rescue strategy to generate high-purity antibodies with substantial cost savings in manufacturing processes.

Glucose phosphorylation by glucokinase exhibits a sigmoidal dependency on substrate concentration regardless of its simple structure. Dimorph mechanism suggested the existence of two enzymatic states with different catalytic properties, which has been shown to be plausible by structural analysis. However, the dimorph mechanism gives rise to a complicated or non-explicit non-closed mathematical form. It is neither feasible to apply the dimorph mechanism in effector characterizations. To improve the area of glucokinase study with stronger theoretical support and less complication in computation, we proposed the investigation of the enzyme from a pseudo-dimeric angle. The proposed mechanism started from the idealization of two monomeric glucokinase as a dimeric complex, which significantly simplified the glucose phosphorylation kinetics, while the differences in enzyme reconfiguration caused by variable substrates and effectors have been successfully characterized. The study presented a simpler and more reliable way in studying the properties of glucokinase and its effectors, providing guidelines of effector developments for hyperglycemia and hypoglycemia treatment.

A liquid-gas two-phase computational fluid dynamics (CFD) model was developed to simulate flow field and gas hold-up in a pilot-scale oxidation ditch (OD). The volume of fluid (VOF) model and the mass flow inlet boundary condition for gas injection were introduced in this model. The simulated values of the flow velocities and the gas hold-up were verified by experimental measurements in the pilot-scale OD. The results showed that the gas hold-up at test-site 3, immediately downstream of the surface aerator, was the highest among all three test-sites. Most of the gas existed in the upper portion of the ditch and was close to the inner side of the channel. Based on the liquid-gas two-phase CFD model, three operating conditions with different setting height ratios of the submerged impellers were simulated. The simulated results suggested that the setting heights of the submerged impellers have significant impacts on the flow velocity distribution. Lowering the setting height could increase the flow velocity in the pilot-scale OD. An optimal setting height ratio of 0.273 was proposed, which would be beneficial for minimizing sludge sedimentation, especially near the inner side of the curve bend.

We present blind predictions using the solubility parameter based method MOSCED submitted for the SAMPL5 challenge on calculating cyclohexane/water distribution coefficients at 298 K. Reference data to parameterize MOSCED was generated with knowledge only of chemical structure by performing solvation free energy calculations using electronic structure calculations in the SMD continuum solvent. To maintain simplicity and use only a single method, we approximate the distribution coefficient with the partition coefficient of the neutral species. Over the final SAMPL5 set of 53 compounds, we achieved an average unsigned error of [Formula: see text] log units (ranking 15 out of 62 entries), the correlation coefficient (R) was [Formula: see text] (ranking 35), and [Formula: see text] of the predictions had the correct sign (ranking 30). While used here to predict cyclohexane/water distribution coefficients at 298 K, MOSCED is broadly applicable, allowing one to predict temperature dependent infinite dilution activity coefficients in any solvent for which parameters exist, and provides a means by which an excess Gibbs free energy model may be parameterized to predict composition dependent phase-equilibrium.

BiFeO 3 -g-C 3 N 4 nanoscaled composite was prepared with a hydrothermal method and evaluated as a highly efficient photo-Fenton like catalyst under visible light irradiation. The BiFeO 3 -g-C 3 N 4 composite exhibited much stronger adsorption ability to lignin model pollutant (guaiacol) than that of BiFeO 3 , which may be due to the higher specific surface area (BiFeO 3 -g-C 3 N 4 : 35.59m 2 /g>BiFeO 3 : 7.42m 2 /g) and the adsorption form of π-π stack between g-C 3 N 4 and guaiacol. The composite exhibited excellent visible light-Fenton like catalysis activity, being influenced by the solution pH value and the proportions of BiFeO 3 and g-C 3 N 4 nanosheets. Under optimal conditions with visible light irradiation, the BiFeO 3 -g-C 3 N 4 composite yielded fast degradation of guaiacol with an apparent rate constant of 0.0452min -1 , which were 5.21 and 6.80 folds of that achieved by using BiFeO 3 and the mixture of BiFeO 3 and g-C 3 N 4 nanosheets, respectively. The significantly enhanced visible light-Fenton like catalytic properties of the BiFeO 3 -g-C 3 N 4 composite in comparison with that of BiFeO 3 was attributed to a large surface area, much increased adsorption capacity and the semiconductor coupling effect between BiFeO 3 and g-C 3 N 4 in the composite., (Copyright © 2016. Published by Elsevier B.V.)

This study investigated reaction pathway and oxidation mechanisms of dibutyl phthalate (DBP) by persulfate (PS) activated with zero-valent iron (ZVI). The DBP degradation was studied at three pH values (acidic, neutral and basic) in the presence of different organic scavengers. Using a chemical probe method, both sulfate radical (SO4(-)) and hydroxyl radical (·OH) were found to be primary oxidants at pH3.0 and pH7.0, respectively while ·OH was the major specie to oxidize DBP at pH11.0. A similar result was found in an experiment of Electron Spin Resonance spin-trapping where in addition to OH, superoxide radical (O2(-)) was detected at pH11.0. The transformation of degradation products including dimethyl phthalate (DMP), diethyl phthalate (DEP), phthalic anhydride, and acetophenone exhibited diverse variation during the reaction processes. The phthalic anhydride concentration appeared to be maximum at all pHs. Another eleven intermediate products were also found at pH3.0 by GC-MS and HPLC analysis, and their degradation mechanisms and pathways were proposed. It was suggested that dealkylation, hydroxylation, decarboxylation and hydrogen extraction were the dominant degradation mechanisms of DBP at pH3.0., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Lignins are complex and heterogeneous natural polymers in which the major units are characterized by certain prominent interunit linkages. Previous attempts to identify and quantify 4-O-5-linked units in softwood lignins by NMR were not successful. In this work, various lignin model compounds, including the tetramers formed by the 4-O-5-coupling of β-O-4-, β-β-, and β-5-model dimers, were synthesized. Such compounds are better able to model the corresponding structures in lignins than those used previously. 4-O-5-Linked structures could be clearly observed and identified in real softwood lignin samples by comparison of their 2D HSQC NMR spectra with those from the model compounds. When comparing NMR data of phenol-acetylated versus phenol-etherified model compounds with those of acetylated lignins, it was apparent that most of the 4-O-5-linked structures in softwood lignins are present as free-phenolic end units.

The thermogravimetric of sugarcane bagasse pretreated by hot-water has been studied in this paper. Results indicated that residual solid pretreatment by hot water could decrease the activation energy of phase 2 (270-350 °C) obviously, which makes the pyrolysis more energy-saving. By hot water pretreatment, the hemicellulose, especially xylose (9.78%/o.d. dry mass at 170 °C and 1 h) was greatly extracted into hydrolyzates liquor. Greatly minimized hemicellulose waste at low temperature during pyrolysis also agreed with biorefinery concept. Therefore, bagasse with hot-water pretreatment should be a good pyrolysis material for value-added material., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

A kinetic model was developed to characterise the heterogeneous nature of kraft delignification kinetics, taking into account the effect of chip thickness. The final form of the model applied to kraft delignification can be represented by a first-order rate equation with a rate constant inversely proportional to a power function of chip thickness. Published laboratory results from kraft pulping of various lignocellulosic materials were used to validate the model. The outcomes confirm the significant effect of chip thickness on the delignification rate. The resultant model was used to predict the effect of chip thickness on the kappa distribution of kraft pulps.

Octanol-water partition coefficients (K(ow)) of 27 substituted aromatic compounds, including polyhalogenated aromatics, were determined. A molecular connectivity index (MCI), a theoretical linear solvation energy relationship, and a quantum chemical method were applied to model the property and study the partition mechanism. The multiple correction coefficients (r2(adj)) (> or = 0.870) and the standard errors (< or = 0.33) for log K(ow) indicated that the models were successful. Comparing the three models, the MCI method (including the nondisperse force factor) was the most satisfactory. However, the quantum chemical model based on the potential of the negative atomic charge, total energy, and molecular weight revealed that the molecular bulk properties and electrostatic interaction were the most important factors influencing the partition process.